title: Cooperative and directional folding of the preQ1 riboswitch aptamer domain.
abstract: Riboswitches are cis-acting RNA fragments that regulate gene expression by sensing cellular levels of the associated small metabolites. In bacteria, the class I preQ(1) riboswitch allows the fine-tuning of queuosine biosynthesis in response to the intracellular concentration of the queuosine anabolic intermediate preQ(1). When binding preQ(1), the aptamer domain undergoes a significant degree of secondary and tertiary structural rearrangement and folds into an H-type pseudoknot. Conformational "switching" of the riboswitch aptamer domain upon recognizing its cognate metabolite plays a key role in the regulatory mechanism of the preQ(1) riboswitch. We investigate the folding mechanism of the preQ(1) riboswitch aptamer domain using all-atom Go̅-model simulations. The folding pathway of such a single domain is found to be cooperative and sequentially coordinated, as the folding proceeds in the 5' → 3' direction. This kinetically efficient folding mechanism suggests a fast ligand-binding response in competition with RNA elongation.
authors.affiliation: Biophysics and Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Nils G
authors.initials: NG
authors.lastname: Walter
authors.forename: Charles L
authors.initials: CL
authors.lastname: Brooks
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000235:genetics; D001412:Bacillus subtilis / Q000235:genetics; D007700:Kinetics; D009690:Nucleic Acid Conformation; D009704:Nucleoside Q / Q000737:chemistry* / Q000235:genetics; D058928:Riboswitch
chemical_list: D052157:Aptamers, Nucleotide; D058928:Riboswitch; D009704:Nucleoside Q